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Canonical transient receptor potential (TRPC) channels are widely expressed in the brain and play several roles in development and normal neuronal function. In the cerebellum, Purkinje cell TRPC3 channels underlie the slow excitatory postsynaptic potential observed after parallel fiber stimulation. In these cells TRPC3 channel opening requires stimulation of metabotropic glutamate receptor 1, activation of which can also lead to the induction of long term depression (LTD), which underlies cerebellar motor learning. LTD induction requires protein kinase C (PKC) and protein kinase G (PKG) activation, and although PKC phosphorylation targets are well established, virtually nothing is known about PKG targets in LTD. Because TRPC3 channels are inhibited after phosphorylation by PKC and PKG in expression systems, we examined whether native TRPC3 channels in Purkinje cells are a target for PKG or PKC, thereby contributing to cerebellar LTD. We find that in Purkinje cells, activation of TRPC3-dependent currents is not inhibited by conventional PKC or PKG to any significant extent and that inhibition of these kinases does not significantly impact on TRPC3-mediated currents either. Based on these and previous findings, we propose that TRPC3-dependent currents may differ significantly in their regulation from those overexpressed in expression systems.

Original publication

DOI

10.1074/jbc.M111.246553

Type

Journal article

Journal

J Biol Chem

Publication Date

24/02/2012

Volume

287

Pages

6326 - 6335

Keywords

Animals, Cerebellum, Cyclic GMP-Dependent Protein Kinases, HEK293 Cells, Humans, Ion Channel Gating, Long-Term Synaptic Depression, Mice, Mice, Inbred C57BL, Organ Culture Techniques, Phosphorylation, Protein Kinase C, Purkinje Cells, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Signal Transduction, Synapses, TRPC Cation Channels